■研究CD40-CD40配体(CD40L)途径在调节弹性蛋白肽(EP)诱导的自身免疫性肺气肿小鼠模型中Th1,Th17和调节性T(Treg)细胞反应中的作用。
BALB/c小鼠在第0天用EP经鼻处理,在第33天经尾静脉注射抗CD40抗体,并在第40天处死。通过测定肺切片的平均线性截距(MLI)和破坏指数(DI)来评价肺气肿的严重程度。血液中髓样树突状细胞(mDC)和Th1,Th17和Treg细胞的比例,脾,脾和肺通过流式细胞术测定。细胞因子白细胞介素(IL)-6,IL-17,干扰素(IFN)-γ的水平,通过酶联免疫吸附法检测转化生长因子(TGF)-β。如果nγ,IL17a,通过聚合酶链反应检测Rorγt和Foxp3转录水平。
■CD40+mDC在EP刺激的小鼠的肺中积累。用抗CD40抗体阻断CD40-CD40L途径减轻Th1和Th17反应;增加Treg细胞的比例;减少MLI和DI;降低细胞因子IL-6,IL-17和IFN-γ的水平以及Ifnγ的转录水平,IL17a,并上调TGF-β和Foxp3的表达。
■CD40-CD40L通路可能在EP介导的肺气肿中Th1、Th17和Treg细胞失调中起关键作用,可能是一个潜在的治疗靶点。
UNASSIGNED: To investigate the role of the CD40-CD40 ligand (CD40L) pathway in the regulation of Th1, Th17, and regulatory T (Treg)-cell responses in an elastin peptide (EP)-induced autoimmune emphysema mouse model.
UNASSIGNED: BALB/c mice were transnasally treated with EP on day 0, injected intravenously with anti-CD40 antibody via the tail vein on day 33, and sacrificed on day 40. The severity of emphysema was evaluated by determining the mean linear intercept (MLI) and destructive index (DI) from lung sections. The proportions of myeloid dendritic cells (mDCs) and Th1, Th17, and Treg cells in the blood, spleen, and lungs were determined via flow cytometry. The levels of the cytokines interleukin (IL)-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β were detected via enzyme-linked immunosorbent assay. Ifnγ, IL17a, Rorγt and Foxp3 transcription levels were detected via polymerase chain reaction.
UNASSIGNED: CD40+ mDCs accumulated in the lungs of EP-stimulated mice. Blocking the CD40-CD40L pathway with an anti-CD40 antibody alleviated Th1 and Th17 responses; increased the proportion of Treg cells; decreased MLI and DI; reduced the levels of cytokines IL-6, IL-17, and IFN-γ as well as the transcription levels of Ifnγ, IL17a, and Rorγt; and upregulated the expression of TGF-β and Foxp3.
UNASSIGNED: The CD40-CD40L pathway could play a critical role in Th1, Th17 and Treg cell dysregulation in EP-mediated emphysema and could be a potential therapeutic target.